Mice Blessed With 'Oxygen-Sensitive' skin: Study

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A team of researchers has suggested that athletes would have to expose their bodies to lower levels of oxygen, during the Summer Olympic Games in Beijing, to enhance their blood's oxygen-carrying capacity which would perk up their performance.

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In a breakthrough discovery, scientists at the University of California, San Diego have established that skin of mice can sense low levels of oxygen and regulate the production of erythropoietin, or EPO, the hormone that stimulates our bodies to produce red blood cells and allows us to adapt to high-altitude, low-oxygen environments.

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Defying the belief that mammalian skin has no link to the respiratory system, this finding may also benefit humans by helping in the treatment of anaemia and other diseases that require boosting our bodies' ability to produce red blood cells and may help improving the performance of endurance athletes.

"What we found in this study is really something quite unusual. We discovered that mammalian skin, at least in mice, responds to how much oxygen is above it and, by virtue of that response, changes blood flow through the skin. This, in turn, changes one of the most basic responses to low oxygen that we have, which is the production of erythropoietin," said Randall Johnson, a professor of biology at UC San Diego who headed the research study.

The scientists have also claimed this to be an evolutionary trait as mammals evolved from lower forms of vertebrates, such as amphibians like frogs, who have extremely permeable skins to facilitate oxygen diffusion.

"From an evolutionary point of view, the results make sense, considering the important role of the skin for oxygen uptake in amphibians. It will be very interesting to see how these mechanisms work in humans and if, for example, different oxygen levels at the skin could affect how rapidly and how well one adapts to low oxygen in the intensive care unit of a hospital or at high altitude," said Frank Powell, a professor of medicine at UCSD.

While no evidence has been found to establish that mice could breathe through their skin, the new discovery may prove most beneficial to athletes during the Summer Olympic Games in Beijing. This can actually make athletes to opt for new methods to boost red blood cell production other than training at altitude and in low-oxygen tents, the two generally accepted legal methods of boosting red blood cell production. Now with this discovery, runners, swimmers, cyclists and other endurance athletes could boost their own EPO and red blood cell counts by exposing their bodies to low levels of oxygen "or, to obtain the same effect, by merely increasing blood flow through their skin."

"We've discovered a potent physiological trigger that can be enacted or enabled without exogenous sources of EPO. We show in this paper that breathing in one level of oxygen and exposing your body to another level of oxygen is really a potent trigger for the body to produce its own EPO. It's not hard to foresee people taking what we've learned in mice and applying it to humans," said Johnson.

The scientists focused on a protein called hypoxia inducible transcription factor-1, or HIF-1, which gets activated when the demands of our muscular system exceed its available supply of oxygen, as in sprinting for a bus or lifting a heavy object. After knocking out the negative regulator of the HIF-1 gene, the scientists produced tiny mice with skin that look red and flushed. These mice have trouble retaining body heat because a larger proportion of their blood is sent to their skin and cooled. But these mutant mice had extremely high EPO levels-so high that 90 percent of their blood plasma is composed of red blood cells, compared to 40 to 50 percent for normal individuals.

"Their blood is basically paste and their hearts are enlarged as a result. When we found that the EPO was coming from internal organs, not the skin of these mice, we thought there must be some kind of signal from the skin to the internal organs," said Johnson.

The researchers discovered that genetically engineering mutant mice without the gene in their skin cells did not produce extra EPO when their skin was exposed to a chamber filled with 10 percent oxygen, but normal mice did increase the amount of EPO production. This was found to be due to more blood rushing into the skin. By putting on the mouse's skin a nitroglycerine patch, which increases blood flow through the skin, the researchers found that mice could dramatically increase their production of EPO and red blood cells.

"We show in this study that by just putting a little nitroglycerine patch we were able to trigger very big increases in EPO. Whether this turns out to be true for humans, we don't know yet. But potentially this could be a very interesting way to manipulate this pathway. If we put mice that lack a hypoxic response in their skin in a low oxygen chamber more than half of their hypoxic response goes away and that was surprising to us. The skin really is a big contributor to the way the mouse responds to low oxygen," said Johnson.

The scientists also said that their discovery might explain why people in some parts of Nepal, India and Pakistan massage newborn babies in mustard oil, a mild irritant that promotes blood flow through the skin.

"We show in this study that if you paint the skin of a mouse with this mild irritant, mustard oil, it will also trigger EPO release at a somewhat lower level. In India and Pakistan babies are in some communities massaged in mustard oil at birth; and some health workers have been trying to get them to stop this folk tradition. But we show that in mice this increases EPO levels. And since increased EPO levels contribute to increased red blood cell counts one could imagine it being beneficial," Johnson said.

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